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Data on epidemiology and secular trend in primary hyperparathyroidism (PHPT) in adults are relatively limited in Asian countries. This study aims to provide an overview of the secular trends in incidence, clinical characteristics, and treatment patterns of PHPT in South Korea. We used Korea's National Health Insurance Claim database (2005-2020) to identify newly diagnosed PHPT cases. Individuals with age below 19, fewer than 2 E21.0 diagnoses, fewer than 2 PTH measurements, secondary hyperparathyroidism, undergoing dialysis or kidney transplantation within a year of diagnosis, parathyroidectomy (PTX) within a year prior to the diagnosis code, and diagnosis of multiple endocrine neoplasm or parathyroid carcinoma were excluded from the analysis. A total of 6837 patients with PHPT (PTX, n  = 2989; non-surgery, n  = 3848) were compared with 1:10 age- and sex-matched controls (n  = 68 370). The mean age of patients with PHPT was 56.0 years, with 77.4% being women. The annual incidence of PHPT increased from 0.23/100 000 persons in 2005 to 1.75 in 2020, with higher rate in women than in men. Compared with 2005-2010 (n  = 675), the number of newly diagnosed PHPT cases increased up to 3.1-fold (n  = 2119) in 2011-2015 and 6.0-fold (n  = 4043) in 2016-2020 periods. Among all patients with PHPT, 43.7% of patients underwent PTX, with decrement of proportion of bilateral surgery among PTX group across time (11.9% in 2005-2010 to 8.9% in 2016-2020, P for trend.033). Among all patients with PHPT, non-surgery group increased from 41.6% in 2005-2010 to 58.0% in 2016-2020 (P for trend <.001). Patients with PHPT had higher odds of osteoporosis (odds ratio [OR] 7.03), renal stones (OR 10.55), chronic kidney diseases (OR 7.42), and cardiovascular, metabolic, and neurological conditions after adjustment for comorbidity index. In summary, the incidence of PHPT increased from 2005 to 2020 with predominance of non-surgical treatment, which calls for research focus on improving non-surgical management. [ABSTRACT FROM AUTHOR]

Positive associations between physical activity and bone health have been found in population-based studies, however, mostly based on self-reported physical activity. Therefore, we investigated the association between accelerometer-measured physical activity, measured in steps per day and minutes of moderate to vigorous physical activity (MVPA) per day, and total hip areal BMD (aBMD) measured by DXA in a general population, utilizing multiple regression models. The study participants, 1560 women and 1177 men aged 40–84 yr, were part of the seventh survey of the Tromsø Study (2015-2016). In both genders, we found a positive association between the number of daily steps and aBMD adjusted for age, BMI, and smoking status (P  < .001). In women, an increase of 1000 steps per day was associated with 0.005 g/cm2 higher aBMD. For men, a polynomial curve indicated a positive association with aBMD up to 5000 steps per day, plateauing between 5000 and 14 000 steps, and then increasing again. Additionally, MVPA duration was positively associated with aBMD in both women (P  < .001) and men (P  = .004) when adjusted for age, BMI, and smoking status. Specifically, each 60-min increase in daily MVPA was associated with 0.028 and 0.023 g/cm2 higher aBMD in women and men, respectively. Despite positive associations, the clinical impact of physical activity on aBMD in this general population of adults and older adults was relatively small, and a large increase in daily MVPA might not be achievable for most individuals. Therefore, further longitudinal population-based studies incorporating device-based measures of physical activity could add more clarity to these relationships. [ABSTRACT FROM AUTHOR]

Whether simultaneous automated ascertainments of prevalent vertebral fracture (auto-PVFx) and abdominal aortic calcification (auto-AAC) on vertebral fracture assessment (VFA) lateral spine bone density (BMD) images jointly predict incident fractures in routine clinical practice is unclear. We estimated the independent associations of auto-PVFx and auto-AAC primarily with incident major osteoporotic and secondarily with incident hip and any clinical fractures in 11 013 individuals (mean [SD] age 75.8 [6.8] years, 93.3% female) who had a BMD test combined with VFA between March 2010 and December 2017. Auto-PVFx and auto-AAC were ascertained using convolutional neural networks (CNNs). Proportional hazards models were used to estimate the associations of auto-PVFx and auto-AAC with incident fractures over a mean (SD) follow-up of 3.7 (2.2) years, adjusted for each other and other risk factors. At baseline, 17% (n = 1881) had auto-PVFx and 27% (n = 2974) had a high level of auto-AAC (≥ 6 on scale of 0 to 24). Multivariable-adjusted hazard ratios (HR) for incident major osteoporotic fracture (95% CI) were 1.85 (1.59, 2.15) for those with compared with those without auto-PVFx, and 1.36 (1.14, 1.62) for those with high compared with low auto-AAC. The multivariable-adjusted HRs for incident hip fracture were 1.62 (95% CI, 1.26 to 2.07) for those with compared to those without auto-PVFx, and 1.55 (95% CI, 1.15 to 2.09) for those high auto-AAC compared with low auto-AAC. The 5-year cumulative incidence of major osteoporotic fracture was 7.1% in those with no auto-PVFx and low auto-AAC, 10.1% in those with no auto-PVFx and high auto-AAC, 13.4% in those with auto-PVFx and low auto-AAC, and 18.0% in those with auto-PVFx and high auto-AAC. While physician manual review of images in clinical practice will still be needed to confirm image quality and provide clinical context for interpretation, simultaneous automated ascertainment of auto-PVFx and auto-AAC can aid fracture risk assessment. Lay Summary: Individuals with calcification of their abdominal aorta (AAC) and vertebral fractures seen on lateral spine bone density images (easily obtained as part of a bone density test) are much more likely to have subsequent fractures. Prior studies have not shown if both AAC and prior vertebral fracture both contribute to fracture prediction in routine clinical practice. Additionally, a barrier to using these images to aid fracture risk assessment at the time of bone density testing has been the need for expert readers to be able to accurately detect both AAC and vertebral fractures. We have developed automated computer methods (using artificial intelligence) to accurately detect vertebral fracture (auto-PVFx) and auto-AAC on lateral spine bone density images for 11 013 older individuals having a bone density test in routine clinical practice. Over a 5-year follow-up period, 7.1% of those with no auto-PVFx and low auto-AAC, 10.1% of those with no auto-PVFx and high auto-AAC, 13.4% of those with auto-PVFx and low auto-AAC, and 18.0% of those with auto-PVFx and high auto-AAC had a major osteoporotic fracture. Auto-PVFx and auto-AAC, ascertained simultaneously on lateral spine bone density images, both contribute to the risk of subsequent major osteoporotic fractures in routine clinical practice settings. [ABSTRACT FROM AUTHOR]

Both bisphosphonates and denosumab are the mainstays of treatment for osteoporosis to prevent fractures. However, there are still few trials directly comparing the prevention of fractures and the safety of 2 drugs in the treatment of osteoporosis. We aimed to compare the efficacy and safety between denosumab and bisphosphonates using a nationwide claims database. The database was covered with 10 million, 20% of the whole Korean population sampled by age and sex stratification of the Health Insurance Review and Assessment Service in South Korea. Among 228 367 subjects who were over 50 yr of age and taking denosumab or bisphosphonate from January 2018 to April 2022, the analysis was performed on 91 460 subjects after 1:1 propensity score matching. The primary outcome was treatment effectiveness; total fracture, major osteoporotic fracture, femur fracture, pelvic fracture, vertebral fracture, adverse drug reactions; acute kidney injury, chronic kidney disease, and atypical femoral fracture. Total fracture and osteoporotic major fracture, as the main outcomes of efficacy, were comparable in the denosumab and bisphosphonate group (HR 1.06, 95% CI, 0.98–1.15, P = .14; HR 1.13, 95% CI, 0.97–1.32, P = .12, respectively). Safety for acute kidney injury, chronic kidney disease, and atypical femoral fracture also did not show any differences between the 2 groups. In subgroup analysis according to ages, the denosumab group under 70 yr of age had a significantly lower risk for occurrences of acute kidney injury compared to the bisphosphonate group under 70 yr of age (HR 0.53, 95% CI, 0.29–0.93, P = .03). In real-world data reflecting clinical practice, denosumab and bisphosphonate showed comparable effectiveness for total fractures and major osteoporosis fractures, as well as safety regarding acute kidney injury, chronic kidney disease, and atypical femoral fracture. Lay Summary: This study compared the effectiveness and safety of denosumab and bisphosphonates, 2 primary treatments for osteoporosis, using a large South Korean nationwide claims database. Analysis of data from 91 460 individuals over 50 yr old showed no significant difference in preventing fractures or in safety outcomes such as kidney injury and atypical femoral fractures between the 2 drugs. However, among patients under 70, denosumab was associated with a lower risk of acute kidney injury. Overall, both medications demonstrated similar effectiveness and safety in the real-world treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Although clinical trials have shown that denosumab significantly increases bone mineral density at key skeletal sites more than oral bisphosphonates, evidence is lacking from head-to-head randomized trials evaluating fracture outcomes. This retrospective cohort study uses administrative claims data from Medicare fee-for service beneficiaries to evaluate the comparative effectiveness of denosumab vs alendronate in reducing fracture risk among women with PMO in the US. Women with PMO ≥ 66 yr of age with no prior history of osteoporosis treatment, who initiated denosumab (n = 89 115) or alendronate (n = 389 536) from 2012 to 2018, were followed from treatment initiation until the first of a specific fracture outcome, treatment discontinuation or switch, end of study (December 31, 2019), or other censoring criteria. A doubly robust inverse-probability of treatment and censoring weighted function was used to estimate the risk ratio associated with the use of denosumab compared with alendronate for hip, nonvertebral (NV; includes hip, humerus, pelvis, radius/ulna, other femur), non-hip nonvertebral (NHNV), hospitalized vertebral (HV), and major osteoporotic (MOP; consisting of NV and HV) fractures. Overall, denosumab reduced the risk of MOP by 39%, hip by 36%, NV by 43%, NHNV by 50%, and HV fractures by 30% compared with alendronate. Denosumab reduced the risk of MOP fractures by 9% at year 1, 12% at year 2, 18% at year 3, and 31% at year 5. An increase in the magnitude of fracture risk reduction with increasing duration of exposure was also observed for other NV fracture outcomes. In this cohort of almost half-a-million treatment-naive women with PMO, we observed clinically significant reductions in the risk of MOP, hip, NV, NHNV, and HV fractures for patients on denosumab compared with alendronate. Patients who remained on denosumab for longer periods of time experienced greater reductions in fracture risk. Lay Summary: Osteoporosis-related fractures can have a significant impact on the health and quality of life of women with postmenopausal osteoporosis, as well as pose a significant burden to society. Although clinical trials have shown that denosumab is more effective at increasing bone mineral density compared with alendronate, there is a lack of evidence evaluating the fracture risk between these 2 commonly used osteoporosis therapies. In this study using Medicare claims data for almost 500 000 women with postmenopausal osteoporosis with no prior history of osteoporosis medication use, we compared the risk of fracture—an important outcome to patients and health care providers—between denosumab and alendronate. Advanced analytic methods were implemented to ensure the study results were valid and were not unduly influenced by biases common in observational studies. We observed clinically meaningful reductions (from 30% up to 50%) in the risk of hip, nonvertebral, non-hip nonvertebral, hospitalized vertebral, and major osteoporotic fractures for patients treated with denosumab compared with alendronate. Patients who remained on denosumab for longer periods of time experienced greater reductions in fracture risk than those who remained on alendronate. [ABSTRACT FROM AUTHOR]

Background: Most fractures occur in women aged ≥80 years but competing mortality unrelated to fracture may limit the benefit of osteoporosis drug therapy for some women in late life. Our primary aim was to develop separate prediction models for non‐spine fracture (NSF) and mortality before fracture to identify subsets of women with varying fracture versus mortality risks. Methods: Separate prediction models were developed for NSF and mortality before NSF for 4895 women aged ≥80 years enrolled in the Study of Osteoporotic Fractures (SOF) or the Health Aging and Body Composition (HABC) study. Proportional hazards models modified to account for competing mortality were used to identify candidate risk factors for each outcome. Predictors associated with NSF or mortality (p < 0.2) were included in separate competing risk models to estimate the cumulative incidence of NSF and mortality before NSF during 5 years of follow‐up. This process was repeated to develop separate prediction models for hip fracture and mortality before hip fracture. Results: Significant predictors of NSF (race, total hip BMD, grip strength, prior fracture, falls, and use of selective serotonin reuptake inhibitors, benzodiazepines, or oral/transdermal estrogen) differed from predictors of mortality before NSF (age, walking speed, multimorbidity, weight change, shrinking, smoking, self‐rated health, dementia, and use of warfarin). Within nine subsets of women defined by tertiles of risk, 5‐year outcomes varied from 28% NSF and 8% mortality in the high‐risk NSF/low‐risk mortality subset, to 9% NSF and 22% mortality in the low‐risk NSF/high‐risk mortality subset. Similar results were seen for predictors of hip fracture and mortality before hip fracture. Conclusion: Considerable variation in 5‐year competing mortality risk is present among women in late life with similar 5‐year NSF risk. Both fracture risk and life expectancy should inform shared clinical decision‐making regarding initiation or continuation of osteoporosis drug therapy for women aged ≥80 years. [ABSTRACT FROM AUTHOR]

General population studies find that rates of child maltreatment are higher than those identified in the child welfare system. Some modes of administration may result in higher disclosure rates of child maltreatment by respondents. This study assesses differences in characteristics of parents who are recruited using telephone sampling techniques or via the internet and whether the survey was administered by telephone or the web. We have 1599 parent respondents recruited from listed samples and Craigslist advertisements. Surveys were administered via the telephone or online. Survey included measures of parenting behaviours, psychosocial characteristics and demographics for the parent, child and family. Data were analysed using logit multilevel models. We found no differences between mode of administration and our child maltreatment and parenting measures, including physical abuse, corporal punishment and supervisory neglect. Recruitment strategy was not related to leaving a child home alone and corporal punishment. However, we did find that parents recruited by Craigslist use physical abuse more frequently. That we found no difference in use of punitive and neglectful parenting practices by survey mode of administration and recruitment method provides some degree of confidence that survey methods other than random‐digit‐dialling telephone surveys may result in generalizable samples in this age of declining landline use. [ABSTRACT FROM AUTHOR]

Timely administration of denosumab every 6 mo is critical in osteoporosis treatment to avoid multiple vertebral fracture risk upon denosumab discontinuation or delay. This study aimed to estimate the immediate and prolonged impact of the COVID-19 pandemic on the timing of denosumab doses. We identified older adults (≥66 yr) residing in the community who were due to receive denosumab between January 2016 and December 2020 using Ontario Drug Benefit data. We completed an interrupted time-series analysis to estimate the impact of the COVID-19 pandemic (March 2020) on the monthly proportion of on-time denosumab doses (183 +/−30 d). Analyses were stratified by user type: patients due for their second dose (novice users), third or fourth dose (intermediate users), or ≥5th dose (established users). In additional analyses, we considered patients living in nursing homes, switching to other osteoporosis drugs, and reported trends until February 2022. We studied 148 554 patients (90.9% female, mean [SD] age 79.6 [8.0] yr) receiving 648 221 denosumab doses. The average pre-pandemic proportion of on-time therapy was steady in the community, yet differed by user type: 64.9% novice users, 72.3% intermediate users, and 78.0% established users. We identified an immediate overall decline in the proportion of on-time doses across all user types at the start of the pandemic: −17.8% (95% CI, −19.6, −16.0). In nursing homes, the pre-pandemic proportion of on-time therapy was similar across user types (average 83.5%), with a small decline at the start of the pandemic: −3.2% (95% CI, −5.0, −1.2). On-time therapy returned to pre-pandemic levels by October 2020 and was not impacted by therapy switching. Although on-time dosing remains stable as of February 2022, approximately one-fourth of patients in the community do not receive denosumab on-time. In conclusion, although pandemic disruptions to denosumab dosing were temporary, levels of on-time therapy remain suboptimal. [ABSTRACT FROM AUTHOR]

Postfracture survival rates provide prognostic information but are rarely reported along with other mortality outcomes in adults aged ≥50 yr. The timing of survival change following a fracture also needs to be further elucidated. This population-based, matched-cohort, retrospective database study examined 98 474 patients (73% women) aged ≥66 yr with an index fracture occurring at an osteoporotic site (hip, clinical vertebral, proximal non-hip non-vertebral [pNHNV], and distal non-hip non-vertebral [dNHNV]) from 2011 to 2015, who were matched (1:1) to nonfracture individuals based on sex, age, and comorbidities. All-cause 1- and 5-yr overall survival and relative survival ratios (RSRs) were assessed, and time trends in survival changes were characterized starting immediately after a fracture. In both sexes, overall survival was markedly decreased over 6 yr of follow-up after hip, vertebral, and pNHNV fractures, and as expected, worse survival rates were observed in older patients and males. The lowest 5-yr RSRs were observed after hip fractures in males (66–85 yr, 51.9%–63.9%; ≥86 yr, 34.5%), followed by vertebral fractures in males (66–85 yr, 53.2%–69.4%; ≥86 yr, 35.5%), and hip fractures in females (66–85 yr, 69.8%–79.0%; ≥86 yr, 52.8%). Although RSRs did not decrease as markedly after dNHNV fractures in younger patients, relatively low 5-yr RSRs were observed in females (75.9%) and males (69.5%) aged ≥86 yr. The greatest reduction in survival occurred within the initial month after hip, vertebral, and pNHNV fractures, indicating a high relative impact of short-term factors, with survival-reduction effects persisting over time. Therefore, the most critical period for implementing interventions aimed at improving post-fracture prognosis appears to be immediately after a fracture; however, considering the immediate need for introducing such interventions, primary fracture prevention is also crucial to prevent the occurrence of the initial fracture in high-risk patients. [ABSTRACT FROM AUTHOR]

Summary: The purpose of this paper is to describe rates of forearm fractures in adults in Norway 2008–2019. Incidence rate of distal forearm fractures declined over time in both sexes. Forearm fracture constitute a significant health burden and prevention strategies are needed. Purpose: To assess age- and sex-specific incidence rates, and time trends for forearm fractures in Norway, and compare these with incidence rates in other Nordic countries. Methods: Data on all patients aged 20–107 years with forearm fractures treated in Norwegian hospitals from 2008 to 2019 was retrieved from the Norwegian Patient Registry. Fractures were identified based on International Classification of Disease 10th revision code S52. Age- and sex-specific incidence rates and changes in incidence rates were calculated. Results: We identified 181,784 forearm fractures in 45,628,418 person-years. Mean annual forearm fracture incidence rates per 100,000 person-years were 398 (95% CI 390–407) for all, 565 (95% CI 550–580) for women, and 231 (95% CI 228–234) for men above 20 years. Mean annual number of forearm fractures was 15,148 (95% CI 14,575–15,722). From 2008 to 2019, age-adjusted total incidence rates of forearm fractures S52 diagnoses declined by 3.5% (incidence rate ratio (IRR) of 0.997 (95% CI 0.994–0.999)) in men. The corresponding decline in women was not significant (IRR: 0.999 (95% CI 0.997–1.002)). In the same period, the age-adjusted incidence rates of distal forearm fractures declined by 7.0% in men (IRR = 0.930; 95% CI 0.886–0.965) and 4.7% in women (IRR = 0.953; 95% CI 0.919–0.976). The incidence rates of distal forearm fractures were similar to rates in Sweden and Finland. Conclusion: Age-adjusted incidence rates of distal forearm fractures in both sexes declined over time. [ABSTRACT FROM AUTHOR]

Muscle strength and physical performance are associated with incident fractures and mortality. However, their role in the risk of subsequent fracture and postfracture mortality is not clear. We assessed the association between muscle strength (grip strength) and performance (gait speed and chair stands time) and the risk of subsequent fracture and mortality in 830 men with low-trauma index fracture, who participated in the Osteoporotic Fractures in Men (MrOS) USA Study and had their index measurements assessed within 5 years prior to the index fracture. The annual decline in muscle strength and performance following index fracture, estimated using linear mixed-effects regression, was also examined in relation to mortality. The associations were assessed using Cox proportional hazards models adjusted for age, femoral neck bone mineral density (FN BMD), prior fractures, falls, body mass index (BMI), index fracture site, lifestyle factors, and comorbidities. Over a median follow-up of 3.7 (interquartile range [IQR], 1.3-8.1) years from index fracture to subsequent fracture, 201 (24%) men had a subsequent fracture and over 5.1 (IQR, 1.8-9.6) years to death, and 536 (65%) men died. Index measurements were not associated with subsequent fracture (hazard ratios [HRs] ranging from 0.97 to 1.07). However, they were associated with postfracture mortality. HR (95% confidence interval [CI]) per 1 standard deviation (1-SD) decrement in grip strength: HR 1.12 (95% CI, 1.01-1.25) and gait speed: HR 1.14 (95% CI, 1.02-1.27), and 1-SD increment in chair stands time: HR 1.08 (95% CI, 0.97-1.21). Greater annual declines in these measurements were associated with higher mortality risk, independent of the index values and other covariates. HR (95% CI) per 1-SD annual decrement in change in grip strength: HR 1.15 (95% CI, 1.01-1.33) and in gait speed: HR 1.38 (95% CI, 1.13-1.68), and 1-SD annual increment in chair stands time: HR 1.28 (95% CI, 1.07-1.54). Men who were unable to complete one or multiple tests had greater risk of postfracture mortality (24%-109%) compared to those performed all tests. It remains to be seen whether improvement in these modifiable factors can reduce postfracture mortality. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Although the detrimental effects of active smoking on bone health have been widely recognized, the impact of secondhand smoke exposure on fracture risk in non-smokers remains less understood. A total of 4843 nonsmokers aged 40–69 yr, who participated in the Korean Genome and Epidemiology Study from 2001 to 2018, were analyzed. The participants were categorized into two groups based on their exposure status to secondhand smoke: currently exposed and unexposed. The exposure group was subsequently divided into two subgroups based on the median weekly exposure time (high vs low). The incidence of new fractures was determined using self-reported questionnaires. The identified fractures were categorized according to the fracture site: overall, vertebral, hip, non-vertebral, and non-vertebral non-hip fractures. The mean age of the participants was 52.4 yr (84.1% women). Exposure to secondhand smoke was associated with an increased risk of fracture (adjusted hazard ratio [aHR]: 1.27, P =  0.028) after adjusting for multiple covariates including age, sex, BMI, household income, bone density of mid-shaft tibia, C-reactive protein, alcohol consumption, and fracture history. Secondhand smoke remained as a significant risk factor for fracture, independent of the major osteoporotic fracture probabilities estimated using a fracture risk assessment tool (aHR: 1.24, P =  0.038). The high exposure group had higher risk of fracture than that of the unexposed group (aHR: 1.33, P =  0.025), whereas the fracture risk did not differ significantly between low exposure and unexposed groups (aHR: 1.18, P =  0.253), suggesting a potential dose–response relationship. Secondhand smoke showed robust association with increased risk of non-vertebral (aHR: 1.37, P =  0.008) or non-vertebral non-hip fractures (aHR: 1.36, P =  0.013), while its association with vertebral fracture was attenuated (aHR: 1.03, P =  0.908). Secondhand smoke was associated with an elevated risk of fracture in nonsmokers, independent of clinical risk factors. [ABSTRACT FROM AUTHOR]

Mouse models suggest that undercarboxylated osteocalcin (ucOC), produced by the skeleton, protects against type 2 diabetes development, whereas human studies have been inconclusive. We aimed to determine if ucOC or total OC is associated with incident type 2 diabetes or changes in fasting glucose, insulin resistance (HOMA-IR), or beta-cell function (HOMA-Beta). A subcohort (n = 338; 50% women; 36% black) was identified from participants without diabetes at baseline in the Health, Aging, and Body Composition Study. Cases of incident type 2 diabetes (n = 137) were defined as self-report at an annual follow-up visit, use of diabetes medication, or elevated fasting glucose during 8 years of follow-up. ucOC and total OC were measured in baseline serum. Using a case-cohort design, the association between biomarkers and incident type 2 diabetes was assessed using robust weighted Cox regression. In the subcohort, linear regression models analyzed the associations between biomarkers and changes in fasting glucose, HOMA-IR, and HOMA-Beta over 9 years. Higher levels of ucOC were not statistically associated with increased risk of incident type 2 diabetes (adjusted hazard ratio = 1.06 [95% confidence interval, 0.84-1.34] per 1 standard deviation [SD] increase in ucOC). Results for %ucOC and total OC were similar. Adjusted associations of ucOC, %ucOC, and total OC with changes in fasting glucose, HOMA-IR, and HOMA-Beta were modest and not statistically significant. We did not find evidence of an association of baseline undercarboxylated or total osteocalcin with risk of incident type 2 diabetes or with changes in glucose metabolism in older adults. © 2022 American Society for Bone and Mineral Research (ASBMR).

ABSTRACT Amino acids are the building blocks of proteins, and sufficient protein intake is important for skeletal health. We utilized stored serum from the Cardiovascular Health Study in 1992–1993 to examine the relationship between levels of the essential amino acid tryptophan (trp) and its oxidized and nonoxidized metabolites to risk for incident hip fractures and mortality over 12 years of follow‐up. We included 131 persons who sustained a hip fracture during this time period and 131 without a hip fracture over these same 12 years of follow‐up; 58% female and 95% White. Weighted multivariable Cox hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of incident hip fracture associated with a one standard deviation (SD) higher trp or its metabolites exposure. Relative risk regression was used to evaluate the cross‐sectional association of trp and its metabolites with frailty. Higher serum levels of trp were significantly associated with lower risk of incident hip fractures (HR = 0.75 per SD of trp (95% CI 0.57–0.99) but were not significantly associated with mortality or frailty status by Freid's frailty index. There were no statistically significant associations between any of the oxidized or nonoxidized products of trp with incident hip fractures (p ≥ 0.64), mortality (p ≥ 0.20), or cross‐sectional frailty status (p ≥ 0.13) after multiple testing adjustment. Randomized clinical trials examining whether increasing trp intake is beneficial for osteoporosis are needed. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Sleep disturbances are common and may impact fracture risk directly by influencing bone turnover or indirectly through shared risk factors or mediators. To investigate the association between self‐reported sleep disturbances across the menopausal transition (MT) and fractures, we prospectively studied 3101 women enrolled in the Study of Women's Health Across the Nation (SWAN). At each of 14 study visits spaced approximately 18 months apart, a standardized validated scale ascertained trouble falling asleep, waking up several times during the night, and waking up earlier than planned. Two time‐varying exposures were modeled: presence of any of the three disturbances at least three times per week and waking up several times during the night at least three times per week. Base models adjusted for fixed (race/ethnicity, study site) and time‐varying characteristics (age, body mass index, and MT stage). Fully adjusted models also included time‐varying bone beneficial and detrimental medications, smoking, alcohol, physical activity, diabetes, depression and sleep medications, and depressive symptoms. Women who experienced a fracture were more likely to report a greater frequency of having trouble falling asleep, waking up several times, and/or waking up earlier: 35% versus 30% at baseline, p = 0.02. In the base models, women who had any of the three sleep disturbances at least three times per week had a higher risk of any fracture, odds ratio (OR) = 1.23 (95% confidence intervals, 1.02, 1.48) and nontraumatic fracture, OR = 1.36 (1.03, 1.80). These associations were largely attenuated to nonsignificance in the fully adjusted model. Sensitivity analyses limiting our sample to 2315 SWAN women enrolled in the bone mineral density (BMD) centers yielded similar results. Additional adjustment for femoral neck BMD had no effect on our results. In conclusion, self‐reported sleep disturbances were associated with an increased risk of fractures, but these associations likely reflect shared risk factors or factors in the causal pathway. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Fragility fractures, resulting from low‐energy trauma, occur in approximately 1 in 10 Danish women aged 50 years or older. Bilateral oophorectomy (surgical removal of both ovaries) may increase the risk of fragility fractures due to loss of ovarian sex steroids, particularly estrogen. We investigated the association between bilateral oophorectomy and risk of fragility fracture and whether this was conditional on age at time of bilateral oophorectomy, hormone therapy (HT) use, hysterectomy, physical activity level, body mass index (BMI), or smoking. We performed a cohort study of 25,853 female nurses (≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from age 50 years or entry into the cohort, whichever came last, until date of first fragility fracture, death, emigration, or end of follow‐up on December 31, 2018, whichever came first. Cox regression models with age as the underlying time scale were used to estimate the association between time‐varying bilateral oophorectomy (all ages, <51/≥51 years) and incident fragility fracture (any and site‐specific [forearm, hip, spine, and other]). Exposure and outcome were ascertained from nationwide patient registries. During 491,626 person‐years of follow‐up, 6600 nurses (25.5%) with incident fragility fractures were identified, and 1938 (7.5%) nurses had a bilateral oophorectomy. The frequency of fragility fractures was 24.1% in nurses who were <51 years at time of bilateral oophorectomy and 18.1% in nurses who were ≥51 years. No statistically significant associations were observed between bilateral oophorectomy at any age and fragility fractures at any site. Neither HT use, hysterectomy, physical activity level, BMI, nor smoking altered the results. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Low countermovement jump power is associated with prevalent fracture, osteoporosis, and sarcopenia in older adults. However, whether jump power predicts incident fracture risk remains uninvestigated. Data of 1366 older adults in a prospective community cohort were analyzed. Jump power was measured using a computerized ground force plate system. Fracture events were ascertained by follow-up interview and linkage to the national claim database (median follow-up 6.4 years). Participants were divided into normal and low jump power groups using a predetermined threshold (women <19.0 W/kg; men <23.8 W/kg; or unable to jump). Among the study participants (mean age 71.6 years, women 66.3%), low jump power was associated with a higher risk of fracture (hazard ratio [HR] = 2.16 versus normal jump power, p < 0.001), which remained robust (adjusted HR = 1.45, p = 0.035) after adjustment for fracture risk assessment tool (FRAX) major osteoporotic fracture (MOF) probability with bone mineral density (BMD) and Asian Working Group for Sarcopenia (AWGS) 2019 sarcopenia definition. In the AWGS no sarcopenia group, participants with low jump power had a significantly higher risk of fracture than those with normal jump power (12.5% versus 6.7%; HR = 1.93, p = 0.013), comparable to that of possible sarcopenia without low jump power (12.0%). Possible sarcopenia group with low jump power had a similar risk of fracture (19.3%) to sarcopenia group (20.8%). When the definition of sarcopenia was modified with jump power measurement (step-up approach: no sarcopenia to possible sarcopenia; possible sarcopenia to sarcopenia when low jump power present), jump power--modified sarcopenia improved sensitivity (18%-39.3%) to classify individuals who sustained MOF during follow-up to high risk compared with AWGS 2019 sarcopenia, while maintaining positive predictive value (22.3%-20.6%). In summary, jump power predicted fracture risk in community-dwelling older adults independently of sarcopenia and FRAX MOF probabilities, suggesting potential contribution of complex motor function measurement in fracture risk assessment. [ABSTRACT FROM AUTHOR]

Objectives Automatic job coding tools were developed to reduce the laborious task of manually assigning job codes based on free-text job descriptions in census and survey data sources, including large occupational health studies. The objective of this study is to provide a case study of comparative performance of job coding and JEM (Job-Exposure Matrix)-assigned exposures agreement using existing coding tools. Methods We compared three automatic job coding tools [AUTONOC, CASCOT (Computer-Assisted Structured Coding Tool), and LabourR], which were selected based on availability, coding of English free-text into coding systems closely related to the 1988 version of the International Standard Classification of Occupations (ISCO-88), and capability to perform batch coding. We used manually coded job histories from the AsiaLymph case-control study that were translated into English prior to auto-coding to assess their performance. We applied two general population JEMs to assess agreement at exposure level. Percent agreement and PABAK (Prevalence-Adjusted Bias-Adjusted Kappa) were used to compare the agreement of results from manual coders and automatic coding tools. Results The coding per cent agreement among the three tools ranged from 17.7 to 26.0% for exact matches at the most detailed 4-digit ISCO-88 level. The agreement was better at a more general level of job coding (e.g. 43.8–58.1% in 1-digit ISCO-88), and in exposure assignments (median values of PABAK coefficient ranging 0.69–0.78 across 12 JEM-assigned exposures). Based on our testing data, CASCOT was found to outperform others in terms of better agreement in both job coding (26% 4-digit agreement) and exposure assignment (median kappa 0.61). Conclusions In this study, we observed that agreement on job coding was generally low for the three tools but noted a higher degree of agreement in assigned exposures. The results indicate the need for study-specific evaluations prior to their automatic use in general population studies, as well as improvements in the evaluated automatic coding tools. [ABSTRACT FROM AUTHOR]

There is limited evidence regarding which fracture types carry the highest risk for subsequent fracture. The aim of this study was to investigate how the risk of imminent fracture depends on index fracture site. This nationwide retrospective cohort study utilized national registers in Sweden to determine the risk of fracture according to recent (≤2 years) index fracture site and according to an old (>2 years) prevalent fracture compared with the risk observed in controls without a fracture. All Swedes 50 years or older between 2007 and 2010 were included in the study. Patients with a recent fracture were designated a specific fracture group depending on the type of previous fracture. Recent fractures were classified as major osteoporotic fracture (MOF), including fractured hip, vertebra, proximal humerus, and wrist, or non-MOF. Patients were followed until December 31, 2017, censored for death and emigration, and the risk of any fracture and hip fracture was assessed. A total of 3,423,320 persons were included in the study, 70,254 with a recent MOF, 75,526 with a recent non-MOF, 293,051 with an old fracture, and 2,984,489 persons with no previous fracture. The median time of follow-up for the four groups was 6.1 (interquartile range [IQR] 3.0-8.8), 7.2 (5.6-9.4), 7.1 (5.8-9.2), and 8.1 years (7.4-9.7), respectively. Patients with a recent MOF, recent non-MOF, and old fracture had a substantially increased risk of any fracture (hazard ratio [HR] adjusted for age and sex 2.11, 95% confidence interval [CI] 2.08-2.14; HR 2.24, 95% CI 2.21-2.27; and HR 1.77, 95% CI 1.76-1.78, respectively) compared with controls. All recent fractures, MOFs, and non-MOFs, as well as older fractures, increase the risk of subsequent fracture, suggesting that all recent fractures should be included in fracture liaison services and that case-finding strategies for those with older fractures may be warranted to prevent subsequent fractures. [ABSTRACT FROM AUTHOR]

We assessed whether a bone resorption marker, measured early in the menopause transition (MT), is associated with change in femoral neck size and strength during the MT. Higher levels of bone resorption were associated with slower increases in femoral neck size and faster decreases in femoral neck strength.PurposeComposite indices of the femoral neck's ability to withstand compressive (compression strength index, CSI) and impact (impact strength index, ISI) forces integrate DXA-derived femoral neck width (FNW), bone mineral density (BMD), and body size. During the menopause transition (MT), FNW increases, and CSI and ISI decrease. This proof-of-concept study assessed whether a bone resorption marker, measured early in the MT, is associated with rates of change in FNW, CSI and ISI during the MT.MethodsWe used previously collected bone resorption marker (urine collagen type I N-telopeptide [U-NTX]) and femoral neck strength data from 696 participants from the Study of Women's Health Across the Nation (SWAN), a longitudinal study of the MT in a multi-ethnic cohort of community-dwelling women.ResultsAdjusted for MT stage (pre- vs. early perimenopause), age, body mass index (BMI), bone resorption marker collection time, and study site in multivariable linear regression, bone resorption in pre- and early perimenopause was not associated with transmenopausal decline rate in femoral neck BMD. However, each standard deviation (SD) increase in bone resorption level was associated with 0.2% per year slower increase in FNW (p = 0.03), and 0.3% per year faster declines in CSI (p = 0.02) and ISI (p = 0.01). When restricted to women in early perimenopause, the associations of bone resorption with change in FNW, CSI, and ISI were similar to those in the full sample.ConclusionsMeasuring a bone resorption marker in pre- and early perimenopause may identify women who will experience the greatest loss in bone strength during the MT.

Demographic and early‐life socioeconomic and parental investment factors may influence later‐life health and development of chronic and progressive diseases, including osteoporosis, a costly condition common among women. The "long arm of childhood" literature links negative early‐life exposures to lower socioeconomic attainment and worse adult health. We build on a small literature linking childhood socioeconomic status (SES) and bone health, providing evidence of whether associations exist between lower childhood SES and maternal investment and higher risk of osteoporosis diagnosis. We further examine whether persons identifying with non‐White racial/ethnic groups experience underdiagnosis. Data from the nationally representative, population‐based cohort Health and Retirement Study (N = 5,490–11,819) were analyzed for participants ages 50–90 to assess these relationships. Using a machine learning algorithm, we estimated seven survey‐weighted logit models. Greater maternal investment was linked to lower odds of osteoporosis diagnosis (odds ratio [OR] = 0.80, 95% confidence interval [CI] = 0.69, 0.92), but childhood SES was not (OR = 1.03, 95% CI = 0.94, 1.13). Identifying as Black/African American (OR = 0.56, 95% CI = 0.40, 0.80) was associated with lower odds, and identifying as female (OR = 7.22, 95% CI = 5.54, 9.40) produced higher odds of diagnosis. There were differences in diagnosis across intersectional racial/ethnic and sex identities, after accounting for having a bone density scan, and a model predicting bone density scan receipt demonstrated unequal screening across groups. Greater maternal investment was linked to lower odds of osteoporosis diagnosis, likely reflecting links to life‐course accumulation of human capital and childhood nutrition. There is some evidence of underdiagnosis related to bone density scan access. Yet results demonstrated a limited role for the long arm of childhood in later‐life osteoporosis diagnosis. Findings suggest that (1) clinicians should consider life‐course context when assessing osteoporosis risk and (2) diversity, equity, and inclusivity training for clinicians could improve health equity. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Denosumab can be used in patients with chronic kidney disease (CKD) but has been linked with cases of severe hypocalcemia. The incidence of and risk factors for hypocalcemia after denosumab use are not well established. Using linked health care databases at ICES, we conducted a population‐based cohort study of adults >65 years old with a new prescription for denosumab or a bisphosphonate between 2012 and 2020. We assessed incidence of hypocalcemia within 180 days of drug dispensing and stratified results by estimated glomerular filtration rate (eGFR in mL/min/1.73 m2). We used Cox proportional hazards to assess risk factors for hypocalcemia. There were 59,151 and 56,847 new denosumab and oral bisphosphonate users, respectively. Of the denosumab users, 29% had serum calcium measured in the year before their prescription, and one‐third had their serum calcium checked within 180 days after their prescription. Mild hypocalcemia (albumin corrected calcium <2.00 mmol/L) occurred in 0.6% (95% confidence interval [CI] 0.6, 0.7) of new denosumab users and severe hypocalcemia (<1.8 mmol/L) in 0.2% (95% CI 0.2, 0.3). In those with an eGFR <15 or receiving maintenance dialysis, the incidence of mild and severe hypocalcemia was 24.1% (95% CI 18.1, 30.7) and 14.9% (95% CI 10.1, 20.7), respectively. In this group, kidney function and baseline serum calcium were strong predictors of hypocalcemia. We did not have information on over‐the‐counter vitamin D or calcium supplementation. In new bisphosphonate users, the incidence of mild hypocalcemia was 0.3% (95% CI 0.3, 0.3) with an incidence of 4.7% (95% CI 1.5, 10.8) in those with an eGFR <15 or receiving maintenance dialysis. In this large population‐based cohort, we found that the overall risk of hypocalcemia with new denosumab use was low but increased substantially in those with eGFR <15 mL/min/1.73 m2. Future studies should investigate strategies to mitigate hypocalcemia. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

The Fracture Risk Assessment Tool (FRAX®) was created to predict major osteoporotic fractures (MOF) and hip fractures in the general population. Whether FRAX accurately predicts fractures in men with prostate cancer is unknown. Our objective was to assess the performance of FRAX for predicting incident fractures in men with prostate cancer. Men from the Manitoba Bone Mineral Density (BMD) Registry (1996–2018) with prostate cancer diagnoses in the 3 years prior to dual‐energy X‐ray absorptiometry (DXA) were identified. FRAX scores with and without BMD were calculated. From population‐based healthcare data we identified incident MOF, hip fracture, any osteoporotic fracture and death from the date of BMD testing to March 31, 2018. Cox regression was performed to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) per standard deviation increase in FRAX score. Observed 10‐year probability (estimated with competing risk of mortality) was compared with 10‐year FRAX‐predicted fracture probability to assess calibration. The study population included 684 men with prostate cancer (mean age 74.6 years) and 8608 men without prostate cancer (mean age 65.5 years). FRAX stratified risk for MOF (HR 1.91, 95% CI 1.48–2.45 with BMD; HR 1.96, 95% CI 1.43–2.69 without BMD) and hip fracture (HR 3.37, 95% CI 1.90–6.01 with BMD; HR 4.58, 95% CI 2.17–9.67 without BMD) in men with prostate cancer. There was no effect modification observed with prostate cancer status or current androgen deprivation therapy. Observed 10‐year fracture probability in men with prostate cancer showed good agreement with FRAX with and without BMD included in the calculation (observed/predicted calibration ratios MOF 0.97, hip 1.00 with BMD; MOF 0.92, hip 0.93 with BMD). In conclusion, FRAX reliably predicts incident fractures in men with prostate cancer. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Abstract Sleep disturbances are common and may impact fracture risk directly by influencing bone turnover or indirectly through shared risk factors or mediators. To investigate the association between self‐reported sleep disturbances across the menopausal transition (MT) and fractures, we prospectively studied 3101 women enrolled in the Study of Women's Health Across the Nation (SWAN). At each of 14 study visits spaced approximately 18 months apart, a standardized validated scale ascertained trouble falling asleep, waking up several times during the night, and waking up earlier than planned. Two time‐varying exposures were modeled: presence of any of the three disturbances at least three times per week and waking up several times during the night at least three times per week. Base models adjusted for fixed (race/ethnicity, study site) and time‐varying characteristics (age, body mass index, and MT stage). Fully adjusted models also included time‐varying bone beneficial and detrimental medications, smoking, alcohol, physical activity, diabetes, depression and sleep medications, and depressive symptoms. Women who experienced a fracture were more likely to report a greater frequency of having trouble falling asleep, waking up several times, and/or waking up earlier: 35% versus 30% at baseline, p = 0.02. In the base models, women who had any of the three sleep disturbances at least three times per week had a higher risk of any fracture, odds ratio (OR) = 1.23 (95% confidence intervals, 1.02, 1.48) and nontraumatic fracture, OR = 1.36 (1.03, 1.80). These associations were largely attenuated to nonsignificance in the fully adjusted model. Sensitivity analyses limiting our sample to 2315 SWAN women enrolled in the bone mineral density (BMD) centers yielded similar results. Additional adjustment for femoral neck BMD had no effect on our results. In conclusion, self‐reported sleep disturbances were associated with an increased risk of fractures, but these associations likely reflect shared risk factors or factors in the causal pathway. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

ABSTRACT Fragility fractures, resulting from low‐energy trauma, occur in approximately 1 in 10 Danish women aged 50 years or older. Bilateral oophorectomy (surgical removal of both ovaries) may increase the risk of fragility fractures due to loss of ovarian sex steroids, particularly estrogen. We investigated the association between bilateral oophorectomy and risk of fragility fracture and whether this was conditional on age at time of bilateral oophorectomy, hormone therapy (HT) use, hysterectomy, physical activity level, body mass index (BMI), or smoking. We performed a cohort study of 25,853 female nurses (≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from age 50 years or entry into the cohort, whichever came last, until date of first fragility fracture, death, emigration, or end of follow‐up on December 31, 2018, whichever came first. Cox regression models with age as the underlying time scale were used to estimate the association between time‐varying bilateral oophorectomy (all ages,

Sleep disturbances are common and may influence falls and fracture directly by influencing bone turnover and muscle strength or indirectly through high comorbidity or poor physical function. To investigate the association between self-reported sleep and falls and fractures, we prospectively studied 157,306 women in the Women's Health Initiative (WHI) using information on sleep quality, sleep duration, and insomnia from questionnaires. Annual self-report of falling two or more times (ie, "recurrent falling") during each year of follow-up was modeled with repeated measures logistic regression models fit by generalized estimating equations. Cox proportional hazards models were used to investigate sleep disturbance and time to first fracture. We examined the risks of recurrent falls and fracture by sleep duration with 7 hours as referent. We examined the risks across categories of sleep disturbance, insomnia status, and sleep quality. The average follow-up time was 7.6 years for falls and 12.0 years for fractures. In multivariable adjusted models, including adjustment for comorbidity, medications, and physical function, women who were short (≤5 hours) and long (≥10 hours) sleepers had increased odds of recurrent falls (odds ratio [OR] 1.28; 95% confidence interval [CI], 1.23 to 1.34 and OR 1.25; 95% CI, 1.09 to 1.43, respectively). Poor sleep quality, insomnia, and more sleep disturbances were also associated with an increased odds of recurrent falls. Short sleep was associated with an increased risk of all fractures, and upper limb, lower limb, and central body fractures, but not hip fractures, with hazard ratios ranging from 1.10 to 1.13 (p

Abstract Background To identify factors related to reproductive history and weight change associated with first incident fracture in middle-aged women. Methods In total, 18,326 women from the Malmö Diet and Cancer study were included in this prospective population-based cohort study. Participants were included 1991–1996 and followed to 2016. Using data from the National Patient Registry, linked with every participants’ unique personal identification number, any first fracture affecting spine, thoracic cage, upper and lower extremities was identified. The association of baseline factors with incident fracture risk was analyzed using Cox regression models. Results For participating women, median age 56.0 years, the multivariable Cox regression analysis observed that early menopause (40–44 years) (hazard ratio (HR) 1.14, 95% confidence interval (CI) 1.03–1.27) but not premature menopause

ABSTRACT Demographic and early‐life socioeconomic and parental investment factors may influence later‐life health and development of chronic and progressive diseases, including osteoporosis, a costly condition common among women. The “long arm of childhood” literature links negative early‐life exposures to lower socioeconomic attainment and worse adult health. We build on a small literature linking childhood socioeconomic status (SES) and bone health, providing evidence of whether associations exist between lower childhood SES and maternal investment and higher risk of osteoporosis diagnosis. We further examine whether persons identifying with non‐White racial/ethnic groups experience underdiagnosis. Data from the nationally representative, population‐based cohort Health and Retirement Study (N = 5,490–11,819) were analyzed for participants ages 50–90 to assess these relationships. Using a machine learning algorithm, we estimated seven survey‐weighted logit models. Greater maternal investment was linked to lower odds of osteoporosis diagnosis (odds ratio [OR] = 0.80, 95% confidence interval [CI] = 0.69, 0.92), but childhood SES was not (OR = 1.03, 95% CI = 0.94, 1.13). Identifying as Black/African American (OR = 0.56, 95% CI = 0.40, 0.80) was associated with lower odds, and identifying as female (OR = 7.22, 95% CI = 5.54, 9.40) produced higher odds of diagnosis. There were differences in diagnosis across intersectional racial/ethnic and sex identities, after accounting for having a bone density scan, and a model predicting bone density scan receipt demonstrated unequal screening across groups. Greater maternal investment was linked to lower odds of osteoporosis diagnosis, likely reflecting links to life‐course accumulation of human capital and childhood nutrition. There is some evidence of underdiagnosis related to bone density scan access. Yet results demonstrated a limited role for the long arm of childhood in later‐life osteoporosis diagnosis. Findings suggest that (1) clinicians should consider life‐course context when assessing osteoporosis risk and (2) diversity, equity, and inclusivity training for clinicians could improve health equity. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Considerable uncertainty prevails regarding risk factors for recurrent fracture among older patients with hip fracture. We aimed to investigate the relationship between prefracture stroke history, baseline mobility, and the risk of recurrent hip fracture. This cohort study was based on the Danish Multidisciplinary Hip Fracture Registry, 2011–2018 (n = 48,230). We estimated cumulative incidence (competing risk of death) of recurrent hip fracture and major osteoporotic fractures within 1 and 2 years comparing patients with/without prefracture stroke history. Analyses were performed overall and stratified on baseline mobility status (good mobility: Cumulated Ambulation Score ≥ 5 versus poor mobility: Cumulated Ambulation Score < 5). Using Cox regression, adjusted cause‐specific hazard ratios (HRs) with 95% confidence intervals (CIs) were obtained. The 1‐year cumulative incidence was 4.6% (95% CI: 3.9–5.4) among patients with stroke history and 4.3% (95% CI: 4.1–4.5) among patients without stroke history. For patients with good mobility, the cumulative incidence of recurrent hip fracture was 5.8% (95% CI: 4.3–7.5) versus 3.7% (95% CI: 3.4–4.0) for patients with versus without stroke history. Corresponding numbers for patients with poor mobility were 4.4% (95% CI: 3.6–5.5) and 5.0% (95% CI: 4.7–5.3). Stroke history was associated with an adjusted HR of 1.55 (95% CI: 1.15–2.10) for recurrent fracture among patients with good mobility. In contrast, no association was observed among patients with poor mobility (adjusted HR 0.88 [95% CI: 0.70–1.10]). The associations were attenuated after 2 years of follow‐up and for major osteoporotic fractures. In conclusion, stroke history was associated with slightly higher risk of recurrent fracture among patients with first‐time hip fracture in the overall analysis, although the CI included a null result. The association was modified by baseline mobility: Patients with stroke history and good mobility had a markedly higher risk, whereas patients with stroke and poor mobility did not. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Summary: In this prospective study in Swedish elderly men, PAD based on an ABI < 0.9 was associated with an increased risk of hip fracture, independent of age and hip BMD. However, after further adjustments for comorbidity, medications, physical function, and socioeconomic factors, the association diminished and was no longer statistically significant. Introduction: To examine if peripheral arterial disease (PAD) is associated with an increased risk for hip fracture in men independent of hip BMD. Methods: Ankle-brachial index (ABI) was assessed in the Swedish MrOS (Osteoporotic Fractures in Men) study, a prospective observational study including 3014 men aged 69–81 years at baseline. PAD was defined as ABI < 0.90. Incident fractures were assessed in computerized X-ray archives. The risk for hip fractures was calculated using Cox proportional hazard models. At baseline, BMD was assessed using DXA (Lunar Prodigy and Hologic QDR 4500) and functional measurements and blood samples were collected. Standardized questionnaires were used to collect information about medical history, falls, and medication. Results: During 10 years of follow-up, 186 men had an incident hip fracture. The hazard ratio (HR) for hip fracture in men with PAD was 1.70 (95% CI 1.14–2.54), adjusted for age and study site. Additional adjustment for total hip BMD marginally affected this association (HR 1.64; 95% CI 1.10–2.45). In a final multivariate model, the HR attenuated to a non-significant HR 1.38 (95% CI 0.91–2.11) adjusted for age, site, hip BMD, BMI, falls, smoking, eGFR, handgrip strength, walking speed, former hip fracture, antihypertensive treatment, diabetes, education, and history of cardiovascular disease. Conclusion: This study suggests that PAD is associated with an increased risk for hip fracture independently of hip BMD in elderly Swedish men. However, the high frequency of comorbidity and lower physical performance among men with PAD might partly explain this association. [ABSTRACT FROM AUTHOR]

Accelerated bone loss (ABL) shown on routine dual-energy X-ray absorptiometry (DXA) may be accompanied by microarchitectural changes, increased cortical porosity, and lower bone strength. To test this hypothesis, we performed a cross-sectional study and used high-resolution peripheral quantitative computed tomography (HR-pQCT) scans (Scanco Medical AG, Brüttisellen, Switzerland) to measure estimated bone strength and microarchitecture in the distal radius and distal and diaphyseal tibia. We studied 1628 men who attended the year 14 exam of the Osteoporotic Fractures in Men (MrOS) study. We retrospectively characterized areal bone mineral density (aBMD) change from the year 7 to year 14 exam in three categories: "accelerated" loss, ≥10% loss at either the total hip or femoral neck (n = 299, 18.4%); "expected" loss,

This study aimed to explore the relationships of several indicators of cigarette smoking habits (smoking status, pack-years, age at smoking initiation and smoking cessation) with quantitative computed tomographic (QCT)-derived proximal femur bone measures (trabecular vBMD, integral vBMD and the ratio of cortical to total tissue volume (cvol/ivol)) and with subsequent change in these measures over the next five years. A total of 2673 older adults (55.9% women), aged 66-92 years at baseline from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, who had two QCT scans of the hip were studied. In multivariable linear regression models, compared to never-smokers, current smokers had lower cvol/ivol at baseline and former-smokers had poorer measures on all outcomes (lower trabecular vBMD, integral vBMD and cvol/ivol), even when adjusted for several potential confounders. Further, among former smokers, those with higher pack-years had worse bone outcomes and those with longer duration since smoking cessation had better bone health at baseline. Analyses of change in bone measures revealed that compared to never-smokers, current smokers had significantly greater loss of trabecular vBMD, integral vBMD, and cvol/ivol. The regression models included adjustment for sex, age, education, and baseline body mass index, creatinine, % weight change from age 50, 25OHD, physical activity level, high-sensitive C-Reactive protein levels, alcohol and coffee consumption, history of diabetes mellitus, arthritis, and respiratory diseases. In conclusion, both current and former smoking showed adverse associations with bone health assessed with QCT. Results suggest that current smoking in particular may aggravate the rate of bone loss at older age and highlight implications for targeting this risk factor in populations that present higher smoking prevalence and vulnerability to bone fragility.

Several in vitro and animal studies have showed that inflammatory markers play a role in bone remodeling and pathogenesis of osteoporosis. Additionally, some human longitudinal studies showed suggestive associations between elevated inflammatory markers and increased risk of nontraumatic fractures. We examined several inflammatory markers and multiple fracture types in a single study of older individuals with extensive follow-up. We assessed the association of four inflammatory markers with the risk of incident hip fractures among 5265 participants of the Cardiovascular Health Study (CHS) and a composite endpoint of incident fractures of the hip, pelvis, humerus, or proximal forearm in 4477 participants. Among CHS participants followed between 1992 and 2009, we observed 480 incident hip fractures during a median follow-up of 11 years. In the composite fracture analysis cohort of 4477 participants, we observed 711 fractures during a median follow-up of 7 years. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for hip fracture associated with doubling of IL-6 were HR 1.15 (95% CI, 1.02 to 1.30) overall and HR 1.17 (95% CI, 1.01 to 1.35) in women. We also observed a positive association between each unit increase in white blood cell (WBC) count and risk of hip fracture: HR 1.04 (95% CI, 1.01 to 1.06) overall and HR 1.06 (95% CI, 0.95 to 1.20) in women. We observed no significant associations between any of the four inflammatory markers and a composite fracture endpoint. Our findings suggest that chronic inflammatory and immune processes may be related to higher rates of incident hip fractures. © 2017 American Society for Bone and Mineral Research.

Higher selenium status has been associated with lower bone turnover markers (BTM) in epidemiological studies. However, the long‐term impact of selenium supplementation on BTMs has not been studied. We investigated the effects of selenium supplementation on BTMs including osteocalcin (OC), procollagen type I N‐terminal propeptide (PINP), collagen type I cross‐linked C‐telopeptide (CTX), and bone alkaline phosphatase (BALP) in the short (6 months) and long term (5 years). A total of 481 Danish men and women (60–74 years) were randomized to receive placebo‐yeast versus 100, 200, or 300 μg selenium as selenium‐enriched yeast daily for 5 years. Plasma selenium concentration was measured using inductively coupled plasma mass spectrometry, and BTMs were measured in nonfasted samples at baseline, 6 months, and 5 years. Data were analyzed by ANCOVA to investigate the shape of the dose‐response relationships. Covariates included age, body mass index, baseline selenium status, baseline BTM, smoking, alcohol, supplement use, and medication. Plasma selenium concentration (mean 86.5 μg/d at baseline) increased significantly with increasing selenium supplementation to 152.6, 209.1, and 253.7 μg/L after 6 months and remained elevated at 5 years (158.4, 222.4, and 275.9 μg/L for 100, 200, and 300 μg supplemental selenium/d, respectively (p < 0.001)). There was no change in plasma selenium concentration in the placebo‐treated group. There was no significant effect of selenium supplementation on OC (6 months p = 0.37; 5 years p = 0.63), PINP (6 months p = 0.37; 5 years p = 0.79), CTX (6 months p = 0.91; 5 years p = 0.58) or BALP (6 months p = 0.17; 5 years p = 0.53). The relatively replete baseline selenium status in the study participants may explain this lack of effect. Testing in more deficient populations may provide further insights into the impact of selenium supplementation on bone health. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Osteoporosis carries a high medical, economic, and societal burden principally because of the risk of severe fractures. The objective of this cost‐of‐illness study was to describe health resource utilization and associated costs in all patients aged ≥50 years hospitalized for a severe osteoporotic fracture over a 6‐year period (2009 to 2014) in France. Data were extracted from the French national healthcare database (SNDS) on all health care resource utilization between the index date (date of hospitalization for first fracture during the enrollment period) and study end (December 31, 2016) or until the patient died. Costing was restricted to direct costs and determined from the payer perspective. Variables related to costs were identified through multivariate logistic regression analysis. A total of 356,895 patients were included (median follow‐up 39.1 months). In the year after the index fracture, 36,622 patients (10.5%) were rehospitalized for a fracture‐related reason. Only 18,474 (5.3%) underwent bone densitometry and 58,220 (16.7%) received a specific treatment. The total annual per capita osteoporosis‐related cost in the year after the index severe osteoporotic fracture was €18,040 (from €8598 for multiple ribs to €21,085 for hip fracture) of which €17,905 was incurred by fracture‐related costs. The cost incurred by management of osteoporosis was €135. Over years 2 to 5, the mean annual per capita costs of fracture treatment (€806, mostly attributable to the treatment of refractures) continued to dominate those of osteoporosis management (€99). Total annual cost of care was €1260 million (year 2014). Variables associated with higher cost were older age, male sex, site of fracture, a history of prior osteoporotic fracture, and the number of refracture events. The 5‐year cost of severe osteoporotic fractures to the French health care system is high and mostly attributable to the treatment of refractures. Improved fracture prevention measures in patients with osteoporosis is crucial to reduce the economic burden of the disease. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

The knowledge about why hip fracture rates in Norway have declined is sparse. Concurrent with decreasing hip fracture rates, the rates of total hip replacements (THRs) have increased. We wanted to investigate if hip fracture rates continued to decline, and whether the increase in THRs had any influence on this decline, assuming that living with a hip prosthesis precludes fracture of the operated hip. Information on hip fractures in Norway 1999–2019 was available from the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS) hip fracture database and population size were available in official population tables from Statistics Norway. Primary THRs (for any cause except hip fracture) 1989–2019 were obtained from the Norwegian Arthroplasty Register. We calculated the annual age‐standardized incidence rates of hip fracture by sex for the period 1999–2019. The hip fracture rates in a scenario with no hip prostheses were calculated by subtracting 0.5 persons from the population at risk for each prevalent hip prosthesis, considering that each person has two hips at risk of fracture. We estimated how much of the decline could be attributed to the increased prevalence of hip prostheses. From 1999 to 2019, age‐standardized incidence rates of hip fracture decreased by 27% in women and 20% in men. The rates remained stable in those under 70 years and decreased in those 70 years and above. Excluding replaced hips from the population at risk led to higher incidence rates, and this impact was considerably larger at higher ages. The increased prevalence of hip prostheses over the period accounted for approximately 18% (20% in women and 11% in men) of the observed decline in hip fracture rates. In conclusion, the incidence of hip fractures continued to decline, and the increasing number of people living with hip prostheses contributed significantly to the observed declining time trends. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Summary: Scanner mismatch occurs frequently with follow-up dual-energy x-ray absorptiometry (DXA) scans. Nearly one-in-five follow-up DXA scans were conducted on non-cross-calibrated scanners (scanner mismatch) and more than a quarter of patients who had a follow-up DXA scan had experienced scanner mismatch. Introduction: Detecting significant changes in bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) scanners relies on the least significant change (LSC). Results from two different DXA scanners can only be compared, albeit with decreased sensitivity for change, if the LSC between the two scanners has been directly determined through cross-calibration. Performing follow-up DXA scans on non-cross-calibrated scanners (scanner mismatch) has safety and economic implications. This study aims to determine the proportion of scanner mismatch occurring at a population level. Methods: All patients who completed at least two DXA scans between 1 April 2009 and 31 December 2018 in the province of Alberta, Canada, were identified using population-based health services databases. Scanner mismatch was defined as a follow-up DXA scan completed on a DXA scanner that differed from and was not cross-calibrated to the previous DXA scanner. Multivariate logistic regression models were used to assess predictive factors that may contribute to scanner mismatch. Results: A total of 264,866 patients with 470,641 follow-up DXA scans were identified. Scanner mismatch occurred in 18.9% of follow-up DXA scans; 28.7% of patients experienced at least one scanner mismatch. Longer duration between scans (OR 1.25, 95% CI 1.24–1.26) and major osteoporotic fracture history before index scan (OR 1.06, 95% CI 1.03–1.08) increased risk of scanner mismatch. Osteoporosis medication use before index scan (OR 0.89; 95% CI 0.88–0.91), recency of follow-up scans (OR 0.98, 95% CI 0.73–0.98), female sex (OR 0.97, 95% CI 0.94–1.00), and age at last scan (OR 0.99, 95% CI 0.99–1.00) were associated with lower risk of scanner mismatch. Conclusion: Scanner mismatch is a common problem, occurring in one-in-five follow-up DXA scans and affecting more than a quarter of patients. Interventions to reduce this large proportion of scanner mismatch are necessary. [ABSTRACT FROM AUTHOR]

There are limited data describing the epidemiology of vertebral fractures (VF) from resource-limited settings, where the ageing population is growing most rapidly. We aimed to determine the prevalence, incidence, and risk factors for VF in The Gambia, West Africa. The Gambian Bone and Muscle Ageing Study is a prospective observational study in men and women aged 40 years and over. Rural participants had baseline measurements and plasma samples collected and were followed up 6-8 years later; urban participants had a single measurement. DXA scans were obtained to assess areal bone mineral density (aBMD), body composition and VF. Prevalence and incidence were calculated. Risk factors for prevalent and incident fracture were tested using logistic regression, in men and women separately, with and without adjustment for age and BMI. At baseline, 581 individuals (298 women) had useable scans, 214 (127 women) at follow-up. Prevalence of VF was 14.8%. Those with VF were older (65.6(11.2) vs 61.7(12.3) years, P=.01) and had lower aBMD Z-scores. For example, in women, a 1SD increase in femoral neck Z-score resulted in a lower risk of having a prevalent VF (OR [95% CI]) 0.51 [0.38, 0.73]. In men, lumbar spine Z-scores were predictive of prevalent fracture; (0.71 [0.53, 0.97]). The incidence of VF over follow-up was 12.1%. Low BMD and grip strength were associated with the odds of having an incident VF. Given the importance of prevalent VF in predicting future VF and other fragility fractures in other populations, our findings are a major cause for concern. VF prevalence in Gambian older adults is similar to elsewhere despite fractures not being a perceived issue. Risk factors were like those identified elsewhere including age, aBMD and bone resorption. Understanding the impact of these fractures is important in a region where health of the ageing population needs to be prioritized., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Epidural steroid injections (ESIs) are a common and often effective treatment for radicular back pain. While oral glucocorticoids increase fracture incidence, little is known regarding fracture risk after ESI. This study investigated the incidence of fractures among individuals who received ESI and those who did not. We hypothesized that ESI exposure would be associated with an increased incidence of osteoporotic fracture and specifically vertebral fractures. Using 2005-2018 5% Medicare data, individuals with radicular pain who had ≥1 ESI and those who did not (non-ESI) were matched 1:10 by age, sex, and month of radicular pain diagnosis using exposure density sampling (EDS). Using a high-dimensional propensity score (HDPS) calculated based on the top 500 covariates across multiple data dimensions, ESI and non-ESI individuals were matched 1:1. Fractures were identified using validated ICD-9/10 diagnosis codes. Fracture incidence rate (IR) was calculated by group, and hazard ratios (HR) compared using Cox regression. 25 062 ESI patients and 221 735 non-ESI patients who met eligibility criteria were identified using EDS. Mean age was 76 years (74% female). Among ESI-treated individuals, there were 2296 fractures, IR 49.1 (95% CI: 47.2-51.2) per 1000 person years. For non-ESI individuals, there were 11 917 fractures, IR 35.2 (95% CI: 34.5-35.8). Individuals who received ESI had a greater hazard of fracture at typical osteoporotic sites, HR 1.39 (95% CI 1.33-1.46) by EDS and 1.32 (1.12-1.54) by HDPS, and greater hazard of vertebral fracture, 1.54 (1.45-1.64) by EDS and 1.69 (1.38-2.07) by HDPS. Patients who received greater cumulative ESI doses (≥3 in 1 year) had a higher risk of fractures within the first six months of follow-up. ESI exposure in older individuals is associated with an increased risk of fracture, suggesting there may be lasting detrimental skeletal effects of ESI. Further research into strategies to reduce fracture risk in this population is warranted., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A recent study published in the Journal of Bone & Mineral Research explores the potential of using proteomics to predict the risk of fractures. The study conducted a meta-analysis using an aptamer-based assay to identify novel protein biomarkers for hip fractures. The researchers found associations between certain proteins, such as the growth hormone receptor and epidermal growth factor receptor, and reduced hip fracture risk, as well as associations between other proteins and increased hip fracture risk. While the study provides valuable insights, further research is needed to establish causal relationships and determine the predictive power of these associations. [Extracted from the article]

Background: To identify factors related to reproductive history and weight change associated with first incident fracture in middle-aged women.Methods: In total, 18,326 women from the Malmö Diet and Cancer study were included in this prospective population-based cohort study. Participants were included 1991-1996 and followed to 2016. Using data from the National Patient Registry, linked with every participants' unique personal identification number, any first fracture affecting spine, thoracic cage, upper and lower extremities was identified. The association of baseline factors with incident fracture risk was analyzed using Cox regression models.Results: For participating women, median age 56.0 years, the multivariable Cox regression analysis observed that early menopause (40-44 years) (hazard ratio (HR) 1.14, 95% confidence interval (CI) 1.03-1.27) but not premature menopause < 40 years (HR 1.06, 95% CI 0.91-1.24) was associated with future fracture risk. Self-reported weight loss since age 20 was also associated with future fracture risk (HR 1.39, 95% CI 1.17-1.65) whereas a daily alcohol consumption in the third quartile (5.36-11.42 g/day) compared to the lowest quartile (0-0.80 g/day) was associated with decreased future fracture risk (HR 0.88, 95% CI 0.81-0.96). The multivariable Cox regression analysis also observed that increasing age and weight at baseline, current smoking, a positive history of previous fracture and family history of fractures were associated with increased fracture risk whereas an increasing BMI was associated with a decreased fracture risk. No association to parity or period of lactation was observed nor ever-use of oral contraceptives and menopausal hormone therapy.Conclusion: This study shows that early menopause between 40 to 45 years and self-reported weight loss since age of 20 are relevant factors associated with increased fracture risk in middle-aged women. These factors were independent of traditional predictors of fracture risk among women and may be considered in preventive initiatives.Trial Registration: Clinicaltrials.gov with identifier: NCT04151732, since Nov 5th 2018. [ABSTRACT FROM AUTHOR]

Norway is an elongated country with large variations in climate and duration of winter season. It is also a high‐risk country for osteoporotic fractures, in particular hip fractures, which cause high mortality. Although most hip fractures occur indoors, there is a higher incidence of both forearm and hip fractures during wintertime, compared with summertime. In a nationwide longitudinal cohort study, we investigated whether cold ambient (outdoor) temperatures could be an underlying cause of this high incidence and mortality. Hospitalized/outpatient forearm fractures (International Classification of Diseases and Related Health Problems, 10th Revision [ICD‐10] code S52) and hospitalized hip fractures (ICD‐10 codes S72.0–S72.2) from 2008 to 2018 were retrieved from the Norwegian Patient Registry. Average monthly ambient temperatures (degrees Celsius, °C) from the years 2008 to 2018 were provided by the Norwegian Meteorological Institute and linked to the residential area of each inhabitant. Poisson models were fitted to estimate the association (incidence rate ratios [IRRs], 95% confidence intervals [CIs]) between temperature and monthly incidence of total number of forearm and hip fractures. Flexible parametric survival models (hazard ratios [HR], 95% CI) were used to estimate the association between temperature and post–hip fracture mortality, taking the population mortality into account. Monthly temperature ranged from −20.2°C to 22.0°C, with a median of −2.0°C in winter and 14.4°C in summer. At low temperatures (<0°C) compared to ≥0°C, there was a 53% higher risk of forearm fracture (95% CI, 51%–55%) and 21% higher risk of hip fracture (95% CI, 19%–22%), adjusting for age, gender, calendar year, urbanization, residential region, elevation, and coastal proximity. When taking the population mortality into account, the post–hip fracture mortality in both men (HR 1.08; 95% CI, 1.02–1.13) and women (HR 1.09; 95% CI, 1.04–1.14) was still higher at cold temperatures. There was a higher risk of forearm and hip fractures, and an excess post–hip fracture mortality at cold ambient temperatures. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Summary: The association between obesity and fracture was skeletal site-specific with no gender difference. Obesity was associated with a higher risk of proximal humerus fractures but not for wrist or clinical vertebral fractures. Purpose: The association between body mass index (BMI) and the risk of clinical fractures at different sites is unclear. This study aimed to examine associations between BMI and fractures at different sites in Korean men and women. Methods: This study analyzed 285,643 Korean adults (aged 50–80 years) who participated in health examinations from 2002 to 2003 and were followed up until 2015. The incidences of osteoporotic fractures were assessed using the International Classification of Diseases (10th revision; ICD-10) and procedure or radiographic codes. After adjusting for confounders, hazard ratios (HRs) were calculated using Cox proportional hazard models for fracture risk. Results: Site-specific associations between BMI and fractures were found without gender difference. Specifically, an L-shaped association was found for clinical vertebral fractures, wherein the adjusted HRs per 5 kg/m2 increase were 0.80 (95% confidence interval [CI] = 0.76–0.83) in BMI groups < 25 kg/m2 and 0.97 (95% CI = 0.92–1.03) in BMI ≥ 25 kg/m2. A linear inverse correlation for wrist fractures was observed, wherein the HRs were 0.83 (95% CI = 0.81–0.86) per 5 kg/m2 increase. For proximal humerus fractures, a non-linear U-shape association was found, wherein the adjusted HRs per 5 kg/m2 increase were 0.66 (95% CI = 0.50–0.88) in BMI groups < 23 kg/m2 and 1.25 (95% CI = 1.08–1.45) in BMI ≥ 23 kg/m2. Conclusion: Low BMI was a risk factor for all tested fractures. Obesity was a risk factor for proximal humerus fracture, but it is a protective factor for wrist fracture. [ABSTRACT FROM AUTHOR]

Although oral bisphosphonates (BP) are commonly used, there is conflicting evidence for their safety in the elderly. Safety concerns might trump BP use in older patients with complex health needs. Our study evaluated the safety of BP, focusing on severe acute kidney injury (AKI), gastrointestinal ulcer (GI ulcer), osteonecrosis of the jaw (ONJ), and femur fractures. We used UK primary care data (Clinical Practice Research Datalink [CPRD GOLD]), linked to hospital (Hospital Episode Statistics [HES] inpatient) and ONS mortality data. We included all patients aged >65 with complex health needs and no BP use in the year before study start (January 1, 2010). Complex health needs were defined in three cohorts: an electronic frailty index score ≥3 (frailty cohort), one or more unplanned hospitalization/s (hospitalization cohort); and prescription of ≥10 different medicines in 2009 (polypharmacy cohort). Incidence rates were calculated for all outcomes. Subsequently, all individuals who experienced AKI or GI ulcer anytime during follow‐up were included for Self‐Controlled Case Series (SCCS) analyses. Incidence rate ratios (IRRs) were estimated separately for AKI and GI ulcer, comparing event rates between BP‐exposed and unexposed time windows. No SCCS were conducted for ONJ and femur fractures. We identified 94,364 individuals in the frailty cohort, as well as 78,184 and 95,621 persons in the hospitalization and polypharmacy cohorts. Of those, 3023, 1950, and 2992 individuals experienced AKI and 1403, 1019, and 1453 had GI ulcer/s during follow‐up, respectively. Age‐adjusted SCCS models found evidence of increased risk of AKI associated with BP use (frailty cohort: IRR 1.65; 95% confidence interval [CI], 1.25–2.19), but no association with GI ulcers (frailty cohort: IRR 1.24; 95% CI, 0.86–1.78). Similar results were obtained for the hospitalization and polypharmacy cohorts. Our study found a 50% to 65% increased risk of AKI associated with BP use in elderly patients with complex health needs. Future studies should further investigate the risk–benefit of BP use in these patients. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

The menopause transition in women is a period of significant bone loss, with rapid declines in bone mineral density (BMD) commencing a year before the final menstrual period (FMP). Changes in menstrual bleeding patterns cannot reliably tell us if this rapid bone loss has begun or is imminent. We hypothesized that low circulating levels of anti‐Mullerian hormone (AMH), which decline as women approach the FMP, would be associated with future and ongoing rapid bone loss. We used data from The Study of Women's Health Across the Nation, a multisite, multi‐ethnic, prospective cohort study of the menopause transition to test this hypothesis. Adjusted for age, body mass index, race/ethnicity, and study site, every 50% decrement in AMH level in premenopause and early perimenopause was associated with 0.14% per year faster decline over the following 3 to 4 years in lumbar spine BMD and 0.11% per year faster decline in femoral neck BMD (p < 0.001 for both). AMH in late perimenopause was not associated with the rate of future BMD decline. AMH was also associated with the magnitude of ongoing bone loss, measured as percent of peak BMD lost by the end of the next 2 to 3 years. Every 50% decrement in AMH level was associated with 0.22% additional loss in spine BMD in premenopause, 0.43% additional loss in early perimenopause, and 0.50% additional loss in late perimenopause (p < 0.001 for all three). If a woman will lose more of her peak BMD than the site‐specific least significant change (LSC) at either the lumbar spine or femoral neck by the next 2 to 3 years, then AMH below 100 pg/mL will detect it with sensitivity of 50% in premenopause, 80% in early perimenopause, and 98% in late perimenopause. These findings suggest that AMH measurement can help flag women at the brink of significant bone loss for early intervention. © 2022 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Serum proteomics analysis may lead to the discovery of novel osteoporosis biomarkers. The Osteoporotic Fractures in Men (MrOS) study comprises men ≥65 years old in the US who have had repeated BMD measures and have been followed for incident fracture. High-throughput quantitative proteomic analysis was performed on baseline fasting serum samples from non-Hispanic white men using a multidimensional approach coupling liquid chromatography, ion-mobility separation, and mass spectrometry (LC-IMS-MS). We followed the participants for a mean of 4.6 years for changes in femoral neck bone mineral density (BMD) and for incident hip fracture. Change in BMD was determined from mixed effects regression models taking age and weight into account. Participants were categorized into three groups: BMD maintenance (no decline; estimated change ≥0 g/cm2 , n = 453); expected loss (estimated change 0 to 1 SD below the estimated mean change, -0.034 g/cm2 for femoral neck, n = 1184); and accelerated loss (estimated change ≥1 SD below mean change, n = 237). Differential abundance values of 3946 peptides were summarized by meta-analysis to determine differential abundance of each of 339 corresponding proteins for accelerated BMD loss versus maintenance. Using this meta-analytic standardized fold change at cutoffs of ≥1.1 or ≤0.9 (p

UNLABELLED: This study examined trends in osteoporosis and low bone mass in older US adults between 2005 and 2014 using bone mineral density (BMD) data from the National Health and Nutrition Examination Survey (NHANES). Osteoporosis and low bone mass appear to have increased at the femur neck but not at the lumbar spine during this period. INTRODUCTION: Recent preliminary data from Medicare suggest that the decline in hip fracture incidence among older US adults may have plateaued in 2013-2014, but comparable data on BMD trends for this time period are currently lacking. This study examined trends in the prevalence of osteoporosis and low bone mass since 2005 using BMD data from NHANES. The present study also updated prevalence estimates to 2013-2014 and included estimates for non-Hispanic Asians. METHODS: Femur neck and lumbar spine BMD by DXA were available for 7954 adults aged 50 years and older from four NHANES survey cycles between 2005-2006 and 2013-2014. RESULTS: Significant trends (quadratic or linear) were observed for the femur neck (mean T-score and osteoporosis in both sexes; low bone mass in women) but not for the lumbar spine. The trend in femur neck status was somewhat U-shaped, with prevalences being most consistently significantly higher (by 1.1-6.6 percentage points) in 2013-2014 than 2007-2008. Adjusting for changes in body mass index, smoking, milk intake, and physicians diagnosis of osteoporosis between surveys did not change femur neck trends. In 2013-2014, the percent of older adults with osteoporosis was 6% at the femur neck, 8% at the lumbar spine, and 11% at either site. CONCLUSIONS: There was some evidence of a decline in femur neck BMD between 2005-2006 and 2013-2014, but not in lumbar spine BMD. Changes in the risk factors that could be examined did not explain the femur neck BMD trends.

Elevated vertebral bone marrow fat (BMF) among individuals with osteoporosis has been established in histomorphometric studies. Several studies have found a negative correlation between BMF and bone mineral density (BMD) at the spine in men and women across different age groups. Animal studies have also observed bone loss with increased BMF in mice with induced diabetes. Our study objective was to test the hypothesis that the association between BMF and BMD varies by diabetic status. We performed a cross-sectional study of 156 men aged 74-96years from the Osteoporotic Fractures in Men study at the Pittsburgh clinical site. All men had spine BMF scans using proton magnetic resonance spectroscopy and spine and hip BMD scans by dual-energy X-ray absorptiometry. BMF was expressed as lipid to "lipid+water" ratio (%). Men were considered diabetic if they self-reported a physician diagnosis of diabetes, diabetes medication or had a fasting glucose ≥126mg/dl. Men with diabetes (n=38) had a significantly higher spine BMF (58.9 vs. 54.6%, p=0.0035), spine BMD (1.20 vs. 1.10g/cm2, P=0.007) and total hip BMD (1.00 vs. 0.94g/cm2, p=0.04) than those without, while no differences were observed for body weight, body mass index or waist circumference. Pearson correlation tests showed no significant correlation of spine BMF with age or BMD in non-diabetics. Significant inverse correlations were observed between BMF and BMD (-0.30 for femoral neck and -0.39 for total hip) among diabetic men. In conclusion, men with diabetes had a higher BMF compared to non-diabetic men. The correlation between BMF and BMD differed by diabetes status. Further investigation of the association of diabetes with BMF and BMD may provide a better understanding of the high fracture rates among individuals with diabetes despite their higher BMD.

Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n = 15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n = 21,701) and clinical vertebral fracture (n = 5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF] = 3%) was associated with higher vBMD (β = 0.22, p = 1.9 × 10-8 ) and decreased risk of radiographic vertebral fracture (odds ratio [OR] = 0.75; false discovery rate [FDR] p = 0.01). In 1p36.12, rs12742784 (MAF = 21%) was associated with higher vBMD (β = 0.09, p = 1.2 × 10-10 ) and decreased risk of clinical vertebral fracture (OR = 0.82; FDR p = 7.4 × 10-4 ). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (β = 0.28, FDR p = 0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (β = 0.12, FDR p = 1.7 × 10-3 , functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence. © 2016 American Society for Bone and Mineral Research.